Humanin, analogs and cancer treatment methods and uses thereof

Abstract

Described herein are methods of enhancing chemotherapeutic treatment of a hyperproliferative disorder by, in part, administering a composition comprising one or more humanin polypeptides to a subject receiving chemotherapy.

What is claimed is: 
     
       1. A method of treating an adult subject having a metastatic neoplasia, tumor, cancer or malignancy, comprising administering to the adult subject an amount of humanin or a humanin analog and a chemotherapeutic agent sufficient to reduce or inhibit proliferation of the metastatic neoplasia, tumor, cancer or malignancy, wherein (i) the amount of the humanin or the humanin analog is in the range of 0.5 to 15 mg/kg body weight, (ii) the chemotherapeutic agent is a DNA intercalating agent or an alkylating agent, and (iii) the humanin or humanin analog increases efficacy or activity of the chemotherapeutic agent. 
     
     
       2. The method of  claim 1 , wherein the humanin comprises the sequence: MAPRGFSCLLLLTSEIDLPVKRRA (SEQ ID NO:1). 
     
     
       3. The method of  claim 1 , wherein the humanin analog comprises the sequence: MAPRGFSCLLLLTGEIDLPVKRRA (HN-S14G) (SEQ ID NO:2), or any sequence set forth in Tables 1-4. 
     
     
       4. The method of  claim 1 , wherein the chemotherapeutic agent comprises an alkylating agent. 
     
     
       5. The method of  claim 1 , wherein the chemotherapeutic agent comprises a DNA intercalating agent or an agent that attaches to DNA. 
     
     
       6. The method of  claim 1 , wherein the chemotherapeutic agent comprises cyclophosphamide, doxorubicin, azathioprine, cyclosporin A, prednisolone, melphalan, chlorambucil, mechlorethamine, busulphan, methotrexate, 6-mercaptopurine, thioguanine, 5-fluorouracil, cytosine arabinoside, 5-azacytidine (5-AZC) and 5-azacytidine related compounds, bleomycin, actinomycin D, mithramycin, mitomycin C, carmustine, lomustine, semustine, streptozotocin, hydroxyurea, cisplatin, carboplatin, oxiplatin, mitotane, procarbazine, dacarbazine, a taxane, vinblastine, vincristine, dibromomannitol, gemcitabine, Temozolomide, or pemetrexed. 
     
     
       7. The method of  claim 1 , wherein the neoplasia, tumor, cancer or malignancy comprises a solid cellular mass. 
     
     
       8. The method of  claim 1 , wherein the neoplasia, tumor, cancer or malignancy comprises hematopoietic cells. 
     
     
       9. The method of  claim 1 , wherein the neoplasia, tumor, cancer or malignancy comprises a carcinoma, sarcoma, lymphoma, leukemia, adenoma, adenocarcinoma, melanoma, glioma, glioblastoma, medulloblastoma, meningioma, neuroblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, mesothelioma, reticuloendothelial, lymphatic or haematopoietic neoplasia, tumor, cancer or malignancy. 
     
     
       10. The method of  claim 9 , wherein the haematopoietic neoplasia, tumor, cancer or malignancy comprises a myeloma, lymphoma or leukemia. 
     
     
       11. The method of  claim 1 , wherein the neoplasia, tumor, cancer or malignancy comprises a metastatic myeloma. 
     
     
       12. The method of  claim 1 , wherein the neoplasia, tumor, cancer or malignancy comprises a lung, thyroid, head or neck, nasopharynx, throat, nose or sinuses, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, gastrointestinal (mouth, esophagus, stomach, duodenum, ileum, jejunum (small intestine), colon, rectum), genito-urinary tract (uterus, ovary, cervix, endometrial, bladder, testicle, penis, prostate), kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, skin, biliary tract, or hematologic neoplasia, tumor, or cancer. 
     
     
       13. The method of  claim 1 , wherein the method inhibits or reduces relapse or progression of the neoplasia, tumor, cancer or malignancy. 
     
     
       14. The method of  claim 1 , wherein the treatment results in partial or complete destruction of the neoplasia, tumor, cancer or malignancy; stimulating, inducing or increasing necrosis, lysis or apoptosis of the neoplasia, tumor, cancer or malignancy; reducing volume size or cell mass of the neoplasia, tumor, cancer or malignancy; inhibiting or preventing progression or an increase in the neoplasia, tumor, cancer or malignancy volume, mass, size or cell numbers; or prolonging lifespan. 
     
     
       15. The method of  claim 1 , wherein the subject is a mammal. 
     
     
       16. The method of  claim 1 , wherein the subject is a human. 
     
     
       17. The method of  claim 1 , wherein the adult is a fertile adult. 
     
     
       18. The method of  claim 17 , wherein the amount of humanin or a humanin analog administered is an amount sufficient to inhibit a decrease or reduction of fertility due to the administration of the chemotherapeutic agent.